Modelling the DFT structural and reactivity study of feverfew and evaluation of its potential antiviral activity against COVID-19 using molecular docking and MD simulations

Introduction: Lactoperoxidase (LPO) is a member of mammalian heme peroxidase family and is an enzyme of innate immune system. It possesses a covalently linked heme prosthetic group (a derivative of protoporphyrin IX) in its active site. LPO catalyzes the oxidation of halides and pseudohalides in the presence of hydrogen peroxide (H2O2) and shows a broad range of antimicrobial activity. Methods: In this study, we have used two pharmaceutically important drug molecules, namely dapsone and propofol, which are earlier reported as potent inhibitors of LPO. Whereas the stereochemistry and mode of binding of dapsone and propofol to LPO is still not known because of the lack of the crystal structure of LPO with these two drugs. In order to fill this gap, we utilized molecular docking and molecular dynamics (MD) simulation studies of LPO in native and complex forms with dapsone and propofol. Results: From the docking results, the estimated binding free energy (ΔG) of -9.25 kcal/mol (Ki = 0.16 μM) and -7.05 kcal/mol (Ki = 6.79 μM) was observed for dapsone, and propofol, respectively. The standard error of Auto Dock program is 2.5 kcal/mol; therefore, molecular docking results alone were inconclusive. Conclusion: To further validate the docking results, we performed MD simulation on unbound, and two drugs bounded LPO structures. Interestingly, MD simulations results explained that the structural stability of LPO-Propofol complex was higher than LPO-Dapsone complex. The results obtained from this study establish the mode of binding and interaction pattern of the dapsone and propofol to LPO as inhibitors.

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Exploration of interaction behavior between spiro[indene-2,2'-[1,3,5]oxathiazine]-1,3-diones and DNA with the help of DFT, molecular docking, and MD simulations

Journal of Biomolecular Structure and Dynamics ◽

10.1080/07391102.2021.1924266 ◽

2021 ◽

pp. 1-21

Author(s):

Mahboobeh Salehpour ◽

Javad Azizian

Keyword(s):

Molecular Docking ◽

Md Simulations ◽

Interaction Behavior

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Studies on molecular mechanism between SHP2 and pyridine derivatives by 3D-QSAR, molecular docking and MD simulations

Journal of Saudi Chemical Society ◽

10.1016/j.jscs.2021.101346 ◽

2021 ◽

pp. 101346

Author(s):

Fangfang Wang ◽

Wei Yang ◽

Zhonglin Li ◽

Bo Zhou

Keyword(s):

Molecular Docking ◽

Molecular Mechanism ◽

3D Qsar ◽

Md Simulations ◽

Pyridine Derivatives

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Search for active candidates in a range of flavonoids regarding SARS-CoV-2 by the method of molecular docking

10.33920/med-13-2101-02 ◽

2021 ◽

pp. 22-35

Author(s):

Stanislav V. Pechinskii ◽

Eduard T. Oganesyan ◽

Anna G. Kuregyan

Keyword(s):

Molecular Docking ◽

Antiviral Activity ◽

Cost Effective ◽

Structural Features ◽

Biologically Active ◽

Active Structures ◽

Main Protease ◽

Targeted Screening ◽

The Relationship ◽

Structure And Activity

Molecular docking is a convenient and cost-effective tool for targeted screening of biologically active structures. This method makes it possible to reveal the relationship between structure and activity, as well as to search for new active compounds. Due to the fact that the antiviral activity of flavonoids and their derivatives has been shown experimentally and clinically, the study of their antiviral activity against SARS-CoV-2 is a promising study. In an in silico experiment, the possibility of binding 20 flavonoid ligands and the main protease SARS-CoV-2 was studied. The structural features of flavone and flavanone derivatives have been determined, which determine their ability to block the main protease of the SARS-CoV-2 virus. Structures of eight new candidates that bind the main protease SARS-CoV-2, which have the prospect of synthesis and further pharmacological research, have been proposed.

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Antiviral Activity of Dopamine Geldanamycin Hybrids Against Influenza Virus and Association with Molecular Docking Analysis

International Journal of Pharmacology ◽

10.3923/ijp.2021.1.14 ◽

2021 ◽

Vol 17 (1) ◽

pp. 1-14

Author(s):

Thongchai Taechowisa ◽

Tipparat Samsawat ◽

Chanjira Jaramornbu ◽

Weerachai Phutdhawon ◽

Waya S. Phutdhawong Phutdhawon

Keyword(s):

Influenza Virus ◽

Molecular Docking ◽

Antiviral Activity ◽

Docking Analysis ◽

Molecular Docking Analysis

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An Analysis Based on Molecular Docking and Molecular Dynamics Simulation Study of Bromelain as Anti-SARS-CoV-2 Variants

Frontiers in Pharmacology ◽

10.3389/fphar.2021.717757 ◽

2021 ◽

Vol 12 ◽

Cited By ~ 1

Author(s):

Trina Ekawati Tallei ◽

Fatimawali ◽

Afriza Yelnetty ◽

Rinaldi Idroes ◽

Diah Kusumawaty ◽

...

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

Molecular Dynamics Simulation ◽

Three Dimensional ◽

Md Simulations ◽

Inhibitory Effect ◽

Dynamics Simulation ◽

Novel Coronavirus

The rapid spread of a novel coronavirus known as SARS-CoV-2 has compelled the entire world to seek ways to weaken this virus, prevent its spread and also eliminate it. However, no drug has been approved to treat COVID-19. Furthermore, the receptor-binding domain (RBD) on this viral spike protein, as well as several other important parts of this virus, have recently undergone mutations, resulting in new virus variants. While no treatment is currently available, a naturally derived molecule with known antiviral properties could be used as a potential treatment. Bromelain is an enzyme found in the fruit and stem of pineapples. This substance has been shown to have a broad antiviral activity. In this article, we analyse the ability of bromelain to counteract various variants of the SARS-CoV-2 by targeting bromelain binding on the side of this viral interaction with human angiotensin-converting enzyme 2 (hACE2) using molecular docking and molecular dynamics simulation approaches. We have succeeded in making three-dimensional configurations of various RBD variants using protein modelling. Bromelain exhibited good binding affinity toward various variants of RBDs and binds right at the binding site between RBDs and hACE2. This result is also presented in the modelling between Bromelain, RBD, and hACE2. The molecular dynamics (MD) simulations study revealed significant stability of the bromelain and RBD proteins separately up to 100 ns with an RMSD value of 2 Å. Furthermore, despite increases in RMSD and changes in Rog values of complexes, which are likely due to some destabilized interactions between bromelain and RBD proteins, two proteins in each complex remained bonded, and the site where the two proteins bind remained unchanged. This finding indicated that bromelain could have an inhibitory effect on different SARS-CoV-2 variants, paving the way for a new SARS-CoV-2 inhibitor drug. However, more in vitro and in vivo research on this potential mechanism of action is required.

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